What is the recommended titration schedule for Trulicity (dulaglutide)?

Trulicity (Dulaglutide) Titration Schedule

Start at 0.75 mg subcutaneously once weekly, increase to 1.5 mg after at least 4 weeks if additional glycemic control is needed, then escalate in 1.5 mg increments (to 3 mg, then 4.5 mg maximum) with at least 4 weeks between each dose increase. 1

Adult Titration Protocol

The FDA-approved titration schedule is straightforward and time-based:

• Starting dose: 0.75 mg subcutaneously once weekly 1
• First escalation: Increase to 1.5 mg once weekly after at least 4 weeks on 0.75 mg if additional glycemic control is needed 1
• Subsequent escalations: Increase in 1.5 mg increments (1.5 mg → 3 mg → 4.5 mg) after at least 4 weeks on each dose 1
• Maximum dose: 4.5 mg once weekly 1

The decision to escalate should be driven by inadequate glycemic control—specifically when HbA1c remains above individualized targets despite 4+ weeks at the current dose. 2 This "treat-to-target" approach with serial dose titration over weeks to months (not years) optimizes patient outcomes. 2

Pediatric Titration Protocol (Age ≥10 Years)

Pediatric dosing is more limited:

• Starting dose: 0.75 mg subcutaneously once weekly 1
• Maximum dose: 1.5 mg once weekly after at least 4 weeks on 0.75 mg 1
• Higher doses (3 mg and 4.5 mg) are not approved for pediatric patients 1

Renal Dosing Considerations

No dose adjustment of dulaglutide is required regardless of kidney function, making titration straightforward even in patients with moderate-to-severe chronic kidney disease or end-stage renal disease. 3, 2 This is a major advantage over many other antihyperglycemic agents that require complex renal dose adjustments. 3 In the AWARD-7 trial, dulaglutide demonstrated efficacy and safety in patients with stage 3-4 chronic kidney disease without dose modification. 4

Concomitant Medication Adjustments

When escalating dulaglutide, consider dose reductions of concurrent insulin or sulfonylureas to prevent hypoglycemia, as dulaglutide has a low inherent risk of hypoglycemia (4.3-4.4 events per patient per year compared to 9.6 with insulin glargine). 2, 4 Do not use dulaglutide in combination with other GLP-1 receptor agonists or DPP-4 inhibitors. 2

Administration Details

• Administer once weekly, any time of day, with or without food 1
• Inject subcutaneously in the abdomen, thigh, or upper arm, rotating injection sites with each dose 1
• The day of weekly administration can be changed if the last dose was administered 3 or more days before the new day 1

Missed Dose Management

If a dose is missed:

• Administer as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose 1
• If less than 3 days remain, skip the missed dose and administer the next dose on the regularly scheduled day 1

Safety Monitoring During Titration

Monitor for the following during dose escalation:

• Gastrointestinal adverse effects: Nausea (15-21%), diarrhea (6-17%), and vomiting (3-4%) are dose-dependent and most common when initiating or escalating doses 2, 5, 4
• Pancreatitis symptoms: Epigastric pain radiating to the back, as dulaglutide can cause elevation of pancreatic enzymes and acute pancreatitis 2, 6
• Acute gallbladder disease 2
• Thyroid nodules or symptoms: Mass in the neck, dysphagia, dyspnea, persistent hoarseness (though routine calcitonin monitoring is of uncertain value) 2, 1

Cardiovascular Benefits

Dulaglutide significantly reduces major adverse cardiovascular events (MACE) in patients with type 2 diabetes with or without established cardiovascular disease, as demonstrated by the REWIND trial. 2 This cardiovascular benefit supports its use beyond glycemic control alone.

Common Pitfalls to Avoid

• Do not titrate too rapidly: Wait at least 4 weeks between dose increases to assess glycemic response and minimize gastrointestinal side effects 1
• Do not combine with other GLP-1 agonists or DPP-4 inhibitors 2
• Do not mix with insulin: When using with insulin, administer as separate injections (though they can be injected in the same body region if not adjacent) 1
• Do not use in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 1